To our knowledge, this is the first large-scale retrospective cohort investigation in the past decade to examine the association between PeHR and MACE in critically ill patients with underlying heart failure. Based on an analysis of 9,730 patients, we observed a strong association between PeHR and the occurrence of major adverse cardiovascular events. This conclusion remained robust even after adjusting for confounders. These findings suggest PeHR may serve as an independent prognostic indicator influencing clinical decision-making in this high-risk population.
The association between in-hospital heart rate regulation and prognosis in heart failure patients has been well-established across multiple studies [15–17], and is explicitly endorsed in recent international guidelines, which emphasize that systematic heart rate monitoring and strict control in heart failure patients carries significant clinical value [18][19]. β-blockers improve clinical outcomes through diverse mechanisms, including reducing sympathetic tone, decelerating heart rate, diminishing myocardial oxygen consumption, and preventing arrhythmias [20][21]. Böhm et al. confirmed that resting heart rate serves as an independent prognostic factor in patients with advanced heart failure, while heart rate reduction correlates with cardiac function recovery and ejection fraction improvement [6]. Faragli et al. demonstrated that a discharge heart rate ≥ 90 beats/min significantly elevates cardiovascular mortality risk, and that β-blocker therapy reduces the composite endpoint of cardiovascular death and rehospitalization at 6 months in patients with acute decompensated heart failure [22]. Takahama and Tsai et al. further illustrated that both in-hospital heart rate decline and optimized post-discharge heart rate control contribute to reducing long-term cardiovascular events and all-cause mortality[23][24]. Our study corroborates these findings. Notably, in our baseline characteristics, despite the PeHR group being younger, they exhibited paradoxically worse overall outcomes, underscoring the hazardous nature of PeHR. With respect to MACE occurrence, in the failing heart, sustained tachycardia augments myocardial oxygen consumption while concomitantly shortening diastolic duration, thereby exacerbating myocardial ischemia and precipitating pump failure—thus, PeHR increases MACE incidence. Intriguingly, our subgroup analysis revealed that PeHR was strongly associated with cardiac arrest and cardiac-related death, yet inversely correlated with myocardial infarction detection (OR = 0.84). This apparent paradox may be explained by several considerations: (1) Critically ill CHF patients with PeHR may experience hemodynamic collapse or malignant arrhythmias triggered by excessive sympathetic activation before manifesting the typical biomarker elevations or electrocardiographic changes required for myocardial infarction diagnosis; (2) Patients admitted for acute myocardial infarction typically receive aggressive heart rate control therapies (e.g., β-blockers, ivabradine) and revascularization, which may effectively attenuate PeHR occurrence during subsequent management.Regarding the principle that heart rate control reduces all-cause mortality, our survival analysis highlights the dynamic risk profile of PeHR. The mortality hazard ratio peaked during the first 30 days (HR = 2.35) and attenuated modestly by 90 days (HR = 2.07), reflecting that PeHR exerts its greatest lethal effect during the acute critical illness phase. In the ICU setting, sustained tachycardia primarily represents a compensatory response to underlying pathologies such as hypovolemia, infection, or low cardiac output syndrome. In chronic heart failure patients with inherently limited cardiac reserve, this persistent high-energy state rapidly depletes myocardial reserves, culminating in irreversible circulatory failure. Survivors beyond this acute phase likely represent a subset of patients who either successfully compensated or received effective interventions, which explains the modest attenuation of relative risk over time.
The precise mechanisms underlying the association between PeHR and heart failure have not been fully elucidated, but multi-dimensional pathogenic pathways have been proposed. The central hypothesis posits that chronically elevated heart rate not only augments myocardial oxygen consumption but also curtails myocardial perfusion by abbreviating diastole. This "supply-demand mismatch" may precipitate myocardial ischemia, energetic failure, and calcium handling abnormalities. Over time, this process can foster ventricular structural remodeling, culminating in left ventricular dysfunction and potentially evolving into tachycardia-induced cardiomyopathy[25]. Furthermore, elevated resting heart rate is often considered a manifestation of autonomic imbalance—characterized by sympathetic overactivity and diminished vagal protective effects—and may engage in complex interactions with systemic inflammation and endothelial dysfunction[26]. While certain mechanistic aspects remain speculative, it is unequivocal that resting heart rate, as a non-invasive and cost-effective biomarker, not only reflects sympathetic burden and coronary perfusion status but also holds significant prognostic value in the early risk stratification of heart failure.
The innovative finding of this study is the confirmation of a positive gradient relationship between heart rate intensity and MACE risk (P for trend = 0.047). This finding satisfies the Bradford Hill criteria for causality, further supporting that tachycardia is not merely a compensatory epiphenomenon but a lethal determinant of adverse outcomes. ROC analysis further elucidated the clinical utility of PeHR. While the multivariable model incorporating PeHR demonstrated moderate discriminative performance for MACE (AUC = 0.586), it exhibited good discrimination for 30-day ICU mortality (AUC ≈ 0.70). This discrepancy reflects that MACE is a multifactorial composite endpoint, whereas in critically ill ICU patients, PeHR serves not as a diagnostic tool but as a risk marker that more sensitively captures acute hemodynamic volatility and sympathetic storm. Consequently, it is imperative to consider PeHR as a "red alert" indicator of physiologic decompensation in critically ill patients with chronic heart failure.
Subgroup analyses demonstrated that the aforementioned risks were significantly amplified in elderly patients, those with sepsis, and those requiring vasoactive drug support. The association between PeHR and adverse outcomes was most pronounced in patients with sepsis and those receiving vasoactive medications (P < 0.001). In these hemodynamically unstable conditions, tachycardia often represents a compensatory mechanism to maintain cardiac output. Clinically, these findings challenge the "one-size-fits-all" approach to heart rate control. While rate control is beneficial in chronic CHF populations, its application in critically ill patients with PeHR warrants caution. Our data suggest that for CHF patients with PeHR, particularly those with concomitant sepsis or shock, actively investigating and treating the underlying etiology of tachycardia may be more clinically meaningful than simply controlling heart rate, as the latter could induce hemodynamic collapse in hearts with fixed stroke volume and thereby exacerbate MACE occurrence. Consequently, the emergence of PeHR should not be viewed simplistically as an indication to initiate pharmacologic rate-lowering therapy (e.g., β-blockade), but rather as a high-risk warning signal that triggers clinicians to aggressively investigate and address potential precipitating factors (such as inadequate circulating volume, uncontrolled infection, pain, or anxiety). Indiscriminately suppressing heart rate during the compensatory tachycardia stage may disrupt the fragile hemodynamic equilibrium of critically ill patients and precipitate circulatory collapse. Future research must delineate the specific hemodynamic window within which the "tipping point" from compensation to decompensation occurs, and identify when heart rate intervention would be both safe and beneficial.
In summary, our study emphasizes that PeHR is a significant independent predictor of MACE and short-term mortality in critically ill patients with chronic heart failure, exhibiting a clear dose-response relationship. This finding underscores the value of PeHR as a core vital sign, whose abnormal elevation should trigger immediate clinical evaluation and heart rate optimization interventions. Dynamic PeHR monitoring in critically ill patients facilitates early identification of high-risk cohorts for adverse outcomes. Although heart rate control demonstrates important clinical value in this population, the optimal target range requires clarification in future studies. Moreover, PeHR monitoring provides objective prognostic evidence to optimize medical resource allocation, enhance physician-patient communication, and inform follow-up strategy development. Integrating PeHR into routine monitoring systems represents a practical and viable approach to improve management standards and clinical outcomes for critically ill patients with heart failure.